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Cited by 20Advanced Electron Microscopy Techniques and ApplicationsProtein Structure and DynamicsEnzyme Structure and Function

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CryoSTAR: leveraging structural priors and constraints for cryo-EM heterogeneous reconstruction

Open access
Li, Yilai, Zhou, Yi, Yuan, Jing, Ye, Fei, Gu, Quanquan·2024·Nature Methods
DOI 10.1038/s41592-024-02486-1

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Abstract

Resolving conformational heterogeneity in cryogenic electron microscopy datasets remains an important challenge in structural biology. Previous methods have often been restricted to working exclusively on volumetric densities, neglecting the potential of incorporating any preexisting structural knowledge as prior or constraints. Here we present cryoSTAR, which harnesses atomic model information as structural regularization to elucidate such heterogeneity. Our method uniquely outputs both coarse-grained models and density maps, showcasing the molecular conformational changes at different levels. Validated against four diverse experimental datasets, spanning large complexes, a membrane protein and a small single-chain protein, our results consistently demonstrate an efficient and effective solution to conformational heterogeneity with minimal human bias. By integrating atomic model insights with cryogenic electron microscopy data, cryoSTAR represents a meaningful step forward, paving the way for a deeper understanding of dynamic biological processes.

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Citations

Cites

Research works printed but not linked: 32

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Metadata

Authors
Li, Y., Zhou, Y., Yuan, J., Ye, F., & Gu, Q.
Affiliations
ByteDance (China) (CN)
Corresponding author
Gu, Quanquan
ORCID
Venue
Nature Methods
Publisher
Springer Science and Business Media LLC
Published
2024-10-29
Volume
21
Issue
12
Pages
2318-2326
ISSN
  • 1548-7091 (ISSN-L)
  • 1548-7105
DOI
10.1038/s41592-024-02486-1
OpenAlex
W4403873534
Cited by
20
References
3
Citations by year
2026: 8 · 2025: 10 · 2024: 2
FWCI
3.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Methods (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Keywords
conformational heterogeneity, structural priors, coarse-grained models, density maps, deep neural network, membrane proteins, single-chain protein
MeSH terms
Algorithms, Humans, Image Processing, Computer-Assisted, Models, Molecular, Protein Conformation, Software, Cryoelectron Microscopy

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